النتائج 1 إلى 4 من 4



الموضوع: محاضرات علم الادويه (المرحله الثالثه)

  1. #1

    محاضرات علم الادويه (المرحله الثالثه)

    It is now well-established that hypertension confers an increased risk of heart attacks and strokes and that treatment of high blood pressure reduces this risk. We now have a wide variety of antihypertensive agents, although most can be classified into one of five major classes (see Panel 1). Each of these classes has merits and disadvantages, as well as ancillary properties that influence the choice for a particular patient. In addition, many patients require more than one agent to control their blood pressure and thus, the choice of combination therapy, with appropriate synergistic effects of the drugs, becomes similarly important
    Panel 1: main classes of antihypertensive drugs

    Diuretics
    beta-blockers
    Calcium channel blockers
    ACE inhibitors
    alpha1-blockers

    Choice of drug

    With the wide variety of antihypertensive agents available, which is the ideal drug to use? The cynic would argue that the ideal antihypertensive drug does not really exist. However, when assessing those that are available to us, it is important to bear in mind the properties that make up an ideal drug for the control of hypertension. The ideal drug should have a predictable dose-response curve, as well as an acceptable, recognised side effect profile. Blood pressure tends to be highest first thing in the morning and this is when the majority of cardiac events occur and, therefore, 24-hour control has been recognised as important. A short-acting drug, even if taken the evening before, may have worn off by the time the patient rises in the morning, whereas a drug with a longer half-life would still be protecting the patient. A drug with a long half-life also has the advantage of only being taken once daily. This may improve compliance, since up to 30 per cent of patients miss a dose at least weekly.
    As the purpose of treating hypertension is to reduce the incidence of hypertensive complications (particularly coronary heart disease and stroke), the ideal drug should have trial evidence to prove that it achieves these ends, as well as simply lowering blood pressure. This is not to say that other drugs do not prevent complications but simply that the evidence from large-scale trials is not there. Advocates of other drugs can point to reductions in surrogate markers, such as left ventricular hypertrophy (LVH) or reduction of microproteinuria, to indicate their effectiveness. Large scale trials, such as ALLHAT (Antihypertensive and Lipid Lowering Heart Attack Trial) and ASCOT (Anglo-Scandinavian Outcomes Trial), which compare newer drugs, such as calcium channel blockers and the ACE inhibitors, with the well-established ß-blockers and diuretics, are currently in progress.
    Diuretics


    Thiazide diuretics Thiazide diuretics reduce the reabsorption of sodium and chloride in the early part of the distal convoluted tubule of the kidney. This results in the delivery of increased amounts of sodium to the distal tubule, where some of it is exchanged for potassium. The net result is increased excretion of sodium, potassium and water. Circulating volume is diminished, reducing preload on the heart and, thus, cardiac output and blood pressure. With long-term therapy, autoregulation by the body’s own compensatory mechanisms results in vasodilatation, reduction of peripheral vascular resistance and return of the cardiac output to normal. Thiazides also have some direct vasodilatory properties.
    Thiazides are rapidly absorbed orally and produce a prolonged diuresis. They tend to produce a maximal response at relatively low doses, such as 12.5mg hydro-chlorothiazide or 1.25mg bendrofluazide. Further increases in dose simply increase side effects with little further effect on blood pressure. On the whole, standard doses of thiazides lower blood pressure as much as other first-line antihypertensives. In some patient groups, such as blacks and the elderly, the thiazides are particularly efficacious. However, they tend to be less effective in younger, white patients.
    Thiazides are one of the classes of antihypertensive that have been extensively tested in large clinical trials. In early trials, thiazides reduced the incidence of stroke by 40 per cent, although the reduction in coronary heart disease was disappointing. This may have been due to the adverse metabolic effects of the large doses used. More recent trials, using lower doses, have demonstrated impressive reductions in both stroke and coronary heart disease, especially in the elderly.
    There is little to choose between the various thiazides, although it seems prudent to use agents, such as hydrochlorothiazide and bendrofluazide, that have been proved to be effective at low doses in clinical trials. Newer agents, such as indapamide, have fewer metabolic side effects, and may even regress hypertensive LVH on echocardiography. Adverse effects The main concerns about thiazide diuretics are their metabolic side effects, although, at low doses, these are less likely to be a problem. They may cause hypokalaemia due to renal potassium wasting. Hypokalaemia may give rise to ventricular arrhythmias and cause adverse drug effects in patients taking digoxin or drugs that prolong the QT interval on the ECG (eg, class I antiarrhythmics, tricyclic antidepressants, antihistamines).
    Acute gout is another common side effect of thiazides, even in low doses. Hyperuricaemia can be present in about 30 per cent of all hypertensives but it is a poor predictor of acute gout. Impotence may occasionally be a problem.
    Thiazides can increase serum LDL-cholesterol and triglyceride levels but this is much less of a problem with modern low doses. There is also some evidence that diuretics impair glucose tolerance and increase insulin resistance. However, reports of frank diabetes are rare. Although thiazides probably should be avoided as first-line drugs in patients with diabetes and those with hyperlipidaemia, there should be no anxiety about adding them in where necessary. Rarer side effects include nausea, headache, rashes, photosensitivity and blood dyscrasias.
    Other diuretics Loop diuretics act on the ascending limb of the loop of Henle and inhibit the reabsorption of chloride, sodium and potassium. They produce a brisk but short-lived diuresis and are thus unsuitable as first-line agents for hypertension, as they do not provide 24-hour control. However, they do have a role in patients with impaired renal function in whom thiazides are ineffective, and in patients with hypertension resistant to multiple drug therapy, who are often fluid overloaded. Furthermore, they may be synergistic with agents such as the ACE inhibitors.
    Potassium-sparing diuretics, such as amiloride and triamterene, produce little reduction in blood pressure themselves. They may be useful in combination with other diuretics to prevent hypokalaemia. Spironolactone is a specific aldosterone antagonist, with a particular role in primary hyperaldosteronism or Conn’s syndrome. Beta-blockers

    Beta-blockers act by blocking the action of noradrenaline at b adrenoceptors throughout the circulatory system and elsewhere. Their major effect is to slow the heart rate and reduce its force of contraction. beta-blockers also cause some reduction in renin release and central sympathetic tone.
    Beta-blockers may be subdivided according to their ancillary properties. For example, b1 or cardioselective agents, such as atenolol, have less action on b2 receptors in the bronchi and peripheral vessels compared with non-selective agents, such as propranolol. This reduces (but does not abolish) b2 receptor-mediated side effects. Lipid-soluble agents, such as propranolol and metoprolol, cross the blood-brain barrier more readily and are associated with a higher incidence of central side effects. Some beta-blockers, such as pindolol, have intrinsic sympathomimetic activity (ie, they stimulate b receptors when background sympathetic nervous activity is low and block them when background sympathetic nervous activity is high). They, therefore, cause less bradycardia and possibly fewer problems with cold extremities than conventional beta-blockers. However, in practice, they are little used in the treatment of hypertension.
    Labetalol and carvedilol have both a- and b1-blocking properties, causing a reduction in peripheral vascular resistance, as well as slowing the heart rate. In addition to its b1-blocking properties, carvedilol also has antioxidant effects, which give it theoretical advantages in reducing endothelial damage and lowering levels of highly atherogenic oxidised LDL-cholesterol. However, both labetalol and carvedilol have the disadvantage of possessing the side effects of both classes of drug.
    Beta-blockers are useful as first-line antihypertensive agents, although they tend to be less effective in the elderly and in black hypertensives. For the treatment of hypertension it is best to choose a beta-blocker with high cardioselectivity and low lipid solubility to reduce side effects. A long half-life also allows once daily dosing.
    Adverse effects Most of the side effects of beta-blockers are predictable from their mode of action. For example, they slow the rate of conduction at the atrio-ventricular node and are thus contraindicated in patients with second- and third-degree heart block. Sinus bradycardia is common and is not a reason to stop beta-blockers unless the patient is symptomatic or the heart rate falls below 40 beats/minute.
    Even small doses of ß-blockers can cause bronchospasm due to blockade of pulmonary b2 receptors, although the problem is less common with cardioselective agents. Even so, all beta-blockers are contraindicated in asthma. Blockade of b receptors in the peripheral circulation causes vasoconstriction, at least in the immediate term, and the drugs are, therefore, contraindicated in patients with rest ischaemia of the legs. Nevertheless, they are reasonably tolerated in those with lesser degrees of peripheral vascular disease. Lipid-soluble agents can cause central nervous system side effects of insomnia, nightmares and fatigue. Exercise capacity may be reduced by beta-blockers and patients may experience tiredness and fatigue. As with most antihypertensives, impotence has been reported, although rates are little higher than with placebo.
    Like diuretics, ß-blockers can worsen glucose intolerance and hyperlipidaemia. In diabetic patients prone to hypoglycaemia, beta-blockers may, theoretically, reduce the awareness of low blood glucose. Nevertheless, many diabetic hypertensives have good reasons, such as a previous myocardial infarction, to be on a beta-blocker and should not be denied them because of concerns about metabolic side effects.
    Calcium channel blockers

    Calcium channel blockers, otherwise known as calcium antagonists, act by interfering with the action of calcium channels in the cell membrane. This reduces the inflow of calcium, smooth muscle contraction and electrical conductivity.
    Calcium channel blockers may be divided into two classes — the dihydropyridines and the non-dihydropyridines. The dihydropyridines, such as nifedipine and amlodipine, act predominantly by causing peripheral vasodilatation. The non-dihydropyridines, such as verapamil and diltiazem, also slow the heart rate and atrio-ventricular node conduction. All calcium channel blockers are efficacious at reducing blood pressure as single agents.
    The older drugs, such as nifedipine, have short half-lives and may cause rapid vasodilatation, a reflex tachycardia and catecholamine surges. This may increase adverse effects and aggravate myocardial ischaemia. Longer-acting agents, such as amlodipine or slow-release preparations of nifedipine, partially overcome these problems.
    Until lately, the calcium channel blockers lacked trial evidence to support their use in hypertension. In the mid-1990s, a series of pharmacosurveillance case-control studies suggested that the short-acting dihydropyridine drugs (such as nifedipine capsules) actually increased the risk of heart attacks.1 Recent data from the Syst-Eur trial demonstrated that antihypertensive treatment of the elderly with the short-acting dihydropyridine calcium channel blocker, nitrendipine, convincingly reduced strokes and heart attacks, without an increase in conditions previously attributed to the calcium channel blockers, such as tumours, bleeding and non-cardiac death.2
    Adverse effects The main, and most troublesome, side effect of calcium channel blockers is ankle oedema. This is caused by vasodilatation, which also causes headache, flushing and palpitation, especially with short-acting dihydropyridines. Some of these side effects can be offset by combining a calcium channel blocker with a b-blocker.
    Verapamil reduces intestinal motility and, thus, can cause significant constipation. More seriously, it can cause heart block, especially in those with underlying conduction problems. Diltiazem can similarly cause gastrointestinal and conduction problems, although less frequently than verapamil. Verapamil, diltiazem and short-acting dihydropyridines are best avoided in patients with heart failure.
    Alpha-blockers

    The a1 adrenoceptor blockers produce vasodilatation by blocking the action of nor-adrenaline at post-synaptic a1 receptors in both arteries and veins. This results in a fall in peripheral resistance, without a compensatory rise in cardiac output. The prototype a1-blocker — prazosin — is short acting and tends to produce precipitous falls in blood pressure, but the longer acting doxazosin combines the advantage of a more gentle reduction in blood pressure with once daily dosing.
    The a1-blockers produce reductions in blood pressure comparable to first-line antihypertensive drugs. They seem to be particularly useful as a third drug, producing good falls in blood pressure where two agents combined have failed. In contrast to the b-blockers and diuretics, a1-blockers actually produce modest improvements in serum lipids and glucose tolerance but whether this translates into improved outcomes is not known, particularly with the paucity of outcome data with these agents.
    Adverse effects a1-blockers are, on the whole, well tolerated. Their main side effect is postural hypotension, which is more commonly caused by shorter-acting agents. In women, a1-blockers may cause urinary incontinence. In men, they may improve the symptoms of benign prostatic hypertrophy. Like most antihypertensive drugs, a1-blockers can cause headache and fatigue.
    ACE inhibitors

    Angiotensin converting enzyme (ACE) inhibitors have become increasingly popular over the past decade. They work by blocking the renin-angiotensin system, inhibiting the conversion of the inactive angiotensin I to the powerful vasoconstrictor and stimulator of aldosterone release, angiotensin II (see Figure 1). This results in decreased peripheral vascular resistance and also a reduction in the levels of the sodium-retaining hormone — aldosterone.
    [IMG]//www.pjonline.com/Editorial/19990904/pictures/angiotensin.gif[/IMG] Figure 1: The renin-angiotensin systems and its inhibitors


    ACE inhibitors also reduce the breakdown of the vasodilator bradykinin, which may enhance their action but is also responsible for their most troublesome side effect of cough. Furthermore, ACE inhibitors may improve endothelial function and reduce central adrenergic tone. They also have beneficial effects on renal haemodynamics, reducing intraglomerular hypertension, resulting in improvements in proteinuric renal disease. ACE inhibitors are effective as single agents in hypertension. There is generally little to choose between the large number of ACE inhibitors available. Recently, the Captopril Prevention Project (CAPP) study demonstrated that captopril was as effective as traditional antihypertensive agents (mainly thiazides and b-blockers) in preventing adverse outcomes in hypertension.3 Other agents, such as fosinopril, have the advantage of hepatic as well as renal excretion and are (theoretically, at least) less likely to accumulate in patients with renal failure. Perindopril, ramipril and trandolapril are agents with long half-lives, which provide good 24-hour antihypertensive coverage.
    There is useful synergism between the ACE inhibitors and diuretics and between ACE inhibitors and calcium channel blockers. The ACE inhibitors are particularly useful in diabetic hypertensives, in whom they may be renoprotective, as they slow the progression of diabetic nephropathy.4 Furthermore, these agents have shown some benefits in improving diabetic retinopathy and even diabetic neuropathy.5,6 However, the ACE inhibitors tend to be less effective as antihypertensive agents in black/Afro-Caribbean hypertensives and in the elderly, who tend to have lower renin levels than the general population. Nevertheless, this relative ineffectiveness can be overcome by using high doses or adding a diuretic.
    Adverse effectsCough, caused by the inhibition of bradykinin breakdown, is the most common side effect of ACE inhibitors, occurring about five times more often than with placebo. Cough is more common in women and older patients.7 The far more serious, but rare, side effect of the ACE inhibitors is angioedema, which occurs in about 0.1 to 0.2 per cent of patients.
    Dramatic deterioration in renal function can occur in patients with bilateral renal artery stenosis. Serum urea and creatinine should, therefore, be checked before and a few weeks after starting an ACE inhibitor. This should not prevent the use of ACE inhibitors in those with other forms of renal disease. In these patients, ACE inhibitors are often agents of first choice, in view of data showing that they slow the progression of diabetic and non-diabetic nephropathy.
    The ACE inhibitors can cause hyperkalaemia because they reduce aldosterone and, thus, potassium excretion. First-dose hypotension is probably an overstated side effect of ACE inhibitors but large doses of short acting captopril can cause sudden falls in blood pressure, especially in those with volume depletion, such as heart failure patients on large doses of diuretics. Rarer side effects include rash, taste disturbance, blood dyscrasias and a symptom complex that includes fever and vasculitis.
    Angiotensin II antagonists


    Like the ACE inhibitors, these drugs act on the renin-angiotensin system, blocking the action of angiotensin II at its peripheral receptors. As they do not inhibit the breakdown of bradykinin, they do not cause cough. However, they may lack the additional physiological benefits that rises in bradykinin levels may bring. Angiotensin II antagonists have similar physiological effects to ACE inhibitors and produce similar falls in blood pressure. There is synergism of antihypertensive effect with thiazide diuretics. There is also evidence that they may regress LVH and improve proteinuria.8,9
    Adverse effects The main advantage of the angiotensin II antagonists is their apparent lack of side effects. Like the ACE inhibitors, they may cause hyperkalaemia, renal impairment and hypotension but, otherwise, they are almost as well tolerated as placebo. Nevertheless, cases of angioedema have been reported with some of these agents. Older antihypertensive agents


    A number of older antihypertensive drugs still have a role in some special situations (eg, pregnancy) and in resistant hypertension. These drugs are popular in countries where hypertensive patients are on low incomes and have to pay for their own medication, because they are cheap.
    Central alpha-blockers These drugs stimulate central a2 adrenoceptors, resulting in a decrease in central sympathetic tone. This leads to a fall in both cardiac output and peripheral vascular resistance. Examples of such drugs include methyldopa and clonidine. The drugs cause sedation, dry mouth and fluid retention. Methyldopa can also cause autoimmune hepatic derangement and haemolytic anaemia. However, it is safe to use in hypertensive pregnant women and is commonly used in such patients. A new centrally acting drug, moxonidine, acts on central imidazoline receptors and is hoped to have the beneficial effects of centrally-acting drugs, without their side effects.
    Direct vasodilators These agents act directly to relax vascular smooth muscle, thereby reducing peripheral vascular resistance. The resulting activation of the sympathetic nervous system means that they can only successfully be used in combination with drugs that block sympathetic activity. Examples include hydralazine, whose main side effect is a lupus-like syndrome, and minoxidil. Minoxidil causes hair growth, a side effect welcomed by many middle aged men but not by their female counterparts.
    Adrenergic neurone blockers Such agents are now rarely used in the United Kingdom. Reserpine and guanethidine inhibit the release of noradrenaline from peripheral nerves. This reduces sympathetic tone, peripheral vascular resistance and cardiac output. They cause postural hypotension and central nervous system depression. Small doses of reserpine, combined with a diuretic, form an effective regimen and are used when low costs are paramount, especially in developing countries.

    تحياتي ................هاي االمحاضره الاوللى والبقيه ان شاء الله في القريب العاجل

  2. #2
    تاريخ التسجيل
    Feb 2007
    الدولة
    عراقي وافتخر
    المشاركات
    313

    افتراضي

    اويليييييييييييييييييييي ريكوبا هاي شدعوووووووووووه هلكد المحاضره عيوني تعبت ونصه مكدرت اقراهااااااااااا اقرااااا وارجع لي وره عمي همزين متصير انت دكتور وتدرس طلاب حتى والله تشوفهم الويل
    هههههههههههههههههههههههههه
    سلمت يمينك بالعكس محاضره حلوه ونريد المحاضره الثانيه

    تحياتي
    التعديل الأخير تم بواسطة tofe_E ; 10-01-2007 الساعة 10:25 PM

  3. #3
    تاريخ التسجيل
    Feb 2007
    الدولة
    عراقي وافتخر
    المشاركات
    313

    افتراضي

    ولو هاي تعتبر مو طويله بالنسبه لمحضرا ت الكليه بس انت تعرف الواحد من يقره على الحاسب مو مثل ميقره بمحاضره

  4. #4

    افتراضي

    ههههههههههههههه والله صحيح كلش طويله بس هاي الفارما هيج بس احاول محاضراتي الجايه نكون مختصره ومتقراها ومترجع ليوره


ضوابط المشاركة

  • لا تستطيع إضافة مواضيع جديدة
  • لا تستطيع الرد على المواضيع
  • لا تستطيع إرفاق ملفات
  • لا تستطيع تعديل مشاركاتك
  •